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Gene Review

MED14  -  mediator complex subunit 14

Homo sapiens

Synonyms: ARC150, Activator-recruited cofactor 150 kDa component, CRSP complex subunit 2, CRSP150, CRSP2, ...
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Disease relevance of CRSP2

  • DRIP150 coactivates ligand-dependent ERalpha-mediated transactivation in ZR-75 and MDA-MB-231 breast cancer cells transfected with a (luciferase) reporter construct (pERE3) regulated by three tandem estrogen-responsive elements [1].

High impact information on CRSP2

  • In yeast and mammalian cells, TSG101 represses whereas DRIP150 enhances GR AF-1-mediated transactivation [2].
  • We further show that the association between the activation domain of SREBP-1 and mediator is through aa 500 to 824 of DRIP150 [3].
  • In the present study, we show that ISGF3-mediated transcription is dependent on STAT2 interactions with DRIP150, a subunit of the multimeric Mediator coactivator complex [4].
  • Vitamin D receptor-interacting protein 150 (DRIP150) has been identified as part of mediator-like complexes that enhance transcriptional activation of the estrogen receptor (ER) and other nuclear receptors (NRs) [1].
  • By using a squelching assay and specific amino acid point mutations within each alpha-helix, the NIFSEVRVYN (795-804) region was identified as the critical sequence required for the activity of DRIP150 [1].

Biological context of CRSP2

  • However, due to its expression in different tissues and its contribution to transcriptional regulation, CRSP2 may be a candidate for other diseases that map to this region of the X chromosome [5].
  • In the course of our search for the gene responsible for X-linked cone-rod dystrophy (COD1), we constructed a physical map and contig (encompassing the region between DXS556 and DXS228), and identified sequences showing homologies to the expressed sequence tags (ESTs) that matched CRSP2 (EXLM1) transcript [5].
  • Orf1 has sequence similarities to the B2 repetitive element and human CXORF4 (formerly called EXLM1), which escapes X inactivation [6].
  • The conserved amino acid sequences of RGR from various mammals can be compared to the amino acid sequence motif of G protein-coupled receptors [7].
  • Three of the markers (tel-OTC, TRAP170 and (ps)ALDH2- cen) located on the short arm of ECAX and EZHX were found inverted on the long arm of EASX, along with the transposition of the centromere [8].

Anatomical context of CRSP2

  • One of the genes matched a known gene, but the other, termed EXLM1, is novel and is predominantly expressed in cultured lymphocytes and skeletal muscle [9].
  • CONCLUSIONS: Using a Lentivirus-derived gene delivery system, we were able to express high amounts of human RGR protein in the ARPE-19 human RPE cell line [10].
  • Expression of a recombinant human RGR opsin in Lentivirus-transduced cultured cells [10].
  • Exon-skipping variant of RGR opsin in human retina and pigment epithelium [11].
  • METHODS: A human RGR cDNA was cloned into a replication-defective lentiviral vector, and recombinant hRGR-Lentivirus was prepared for transduction of the ARPE-19, a human retinal pigment epithelium (RPE) cell line, and COS-7 cells [10].

Associations of CRSP2 with chemical compounds

  • Coactivation of ERalpha by DRIP150 in ZR-75 cells was activation function 2-dependent and required an intact helix 12 that typically interacts with LXXLL motifs (NR box) in p160 steroid receptor coactivators [1].

Other interactions of CRSP2


  1. DRIP150 coactivation of estrogen receptor alpha in ZR-75 breast cancer cells is independent of LXXLL motifs. Lee, J.E., Kim, K., Sacchettini, J.C., Smith, C.V., Safe, S. J. Biol. Chem. (2005) [Pubmed]
  2. Differential regulation of glucocorticoid receptor transcriptional activation via AF-1-associated proteins. Hittelman, A.B., Burakov, D., Iñiguez-Lluhí, J.A., Freedman, L.P., Garabedian, M.J. EMBO J. (1999) [Pubmed]
  3. Selective coactivator interactions in gene activation by SREBP-1a and -1c. Toth, J.I., Datta, S., Athanikar, J.N., Freedman, L.P., Osborne, T.F. Mol. Cell. Biol. (2004) [Pubmed]
  4. Role of metazoan mediator proteins in interferon-responsive transcription. Lau, J.F., Nusinzon, I., Burakov, D., Freedman, L.P., Horvath, C.M. Mol. Cell. Biol. (2003) [Pubmed]
  5. Refinement of the physical location and the genomic characterization of the CRSP2 (EXLM1) gene on Xp11.4. Demirci, F.Y., Ramser, J., White, N.J., Rigatti, B.W., Meindl, A., Lewis, K.F., Wen, G., Gorin, M.B. DNA Seq. (2003) [Pubmed]
  6. Detection and cloning of an X-linked locus associated with a NotI site that is not methylated on mouse inactivated X chromosome by the RLGS-M method. Takada, S., Kamiya, M., Arima, T., Kagebayashi, H., Shibata, H., Muramatsu, M., Chapman, V.M., Wake, N., Hayashizaki, Y., Takagi, N. Genomics (1999) [Pubmed]
  7. Structure and developmental expression of the mouse RGR opsin gene. Tao, L., Shen, D., Pandey, S., Hao, W., Rich, K.A., Fong, H.K. Mol. Vis. (1998) [Pubmed]
  8. Comparative mapping in equids: the asine X chromosome is rearranged compared to horse and Hartmann's mountain zebra. Raudsepp, T., Lear, T.L., Chowdhary, B.P. Cytogenet. Genome Res. (2002) [Pubmed]
  9. Detection and isolation of a novel human gene located on Xp11.2-p11.4 that escapes X-inactivation using a two-dimensional DNA mapping method. Yoshikawa, H., Fujiyama, A., Nakai, K., Inazawa, J., Matsubara, K. Genomics (1998) [Pubmed]
  10. Expression of a recombinant human RGR opsin in Lentivirus-transduced cultured cells. Yang, M., Wang, X.G., Stout, J.T., Chen, P., Hjelmeland, L.M., Appukuttan, B., Fong, H.K. Mol. Vis. (2000) [Pubmed]
  11. Exon-skipping variant of RGR opsin in human retina and pigment epithelium. Fong, H.K., Lin, M.Y., Pandey, S. Exp. Eye Res. (2006) [Pubmed]
  12. Structure and biological properties of three calcitonin receptor-stimulating peptides, novel members of the calcitonin gene-related peptide family. Katafuchi, T., Minamino, N. Peptides (2004) [Pubmed]
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